(a) Field
The subject matter disclosed generally relates to a pharmaceutical compositions and methods to improve organ function, and more specifically to pharmaceutical compositions and methods to improve organ function with high doses of insulin.
(b) Related Prior Art
Evidence suggests that variability of glycemia, rather than the absolute blood glucose value, are associated with outcomes during, and especially after, surgery. Although hyperglycemia is a well-recognized risk factor in the context of cardiac surgery, the relevance of pre-, peri-, and post-operative glycemic control for patients undergoing major noncardiac operations, such as major surgical resections and organ transplantation from either live or cadaveric donors, has received little attention as hyperglycemia is a reflection of heightened inflammatory response to stress. There is a need for a treatment that targets both inflammatory response and stress
More recent attempts to achieve tight glucose control in critical patients were associated with a significant incidence of hypoglycaemia. For example, the NICE-SUGAR trial (Finfer S, Chittock D R, Su S Y, et al. NEJM 2009; 360:1283-97), a randomized controlled trial involving more than 6000 patients comparing intensive (target blood glucose 81-108 mg/dL) versus conventional (target blood glucose≦180 mg/dL) glucose control, reported a high incidence of severe hypoglycaemia and increased mortality in patients administered with intensive insulin therapy. Therefore, tight glucose control cannot be achieved using the insulin sliding scale together with the occasional measurements of blood glucose. Furthermore, the use of intensive insulin therapy placed critically ill patients with sepsis (VISEP trial) at an increased risk for serious adverse events related to hypoglycaemia. Thus, the benefits of strict glycemic control in the ICU have not been established by either the VISEP or NICE-SUGAR trials. Therefore, there is a need for improved treatment modalities for the control of glycemia
Liver disease related to acute systemic inflammation as in brain-dead organ donors and acute ischemia/reperfusion injury for organ transplants where the inflammatory status can affect graft and recipient survival
Liver disease related to chronic systemic inflammation example of chronic liver disease from hepatitis C viral infection, and non-alcholic fatty liver disease, where liver disease is a part of a systemic inflammation and insulin resistance, increase mobilization of free fatty acid, increase liver steatosis, diminishing liver glycogen content and ending with liver fibrosis, cirrhosis and liver cancer.
There is therefore a need for pharmaceutical compositions and methods to eliminate or at least reduce the levels of pro-inflammatory markers prior to, during, and following surgical intervention.
There is therefore a need for a technique that can achieve a tight glucose control and avoid hypoglycemia in critically ill patients or surgical patients.
There is therefore a need for pharmaceutical compositions and method to eliminate or at least reduce the levels of pro-inflammatory markers associated both acute and chronic inflammatory status e.g. brain death, surgical stress, insulin resistance, fatty liver diseases, and/or chronic viral liver infections.